A fungus is a member of a large group of organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushroom. These organisms are classified as a Kingdom, Fungi, which is separate from plants, animals and bacteria. Before the introduction of molecular methods for phylogenetic analysis, taxonomists considered fungi to be members of the Plant Kingdom primarily because of the similarities in lifestyle, as both fungi and plants are largely immobile, and have similarities in general morphology and growth habitat. Post molecular methods for phylogenetic analysis, the fungi have been a separate Kingdom distinct from both plants and animals, from which they appear to have diverged around one billion years ago. Advances in molecular genetics have opened the door for DNA analysis to be incorporated into taxonomy, which has oftentimes challenged the historical groupings of fungi based on morphology and other traits. Phylogenetic studies published in the last decade have helped reshape the classification of the Kingdom Fungi, which is divided into one subkingdom, seven phyla, and ten subphyla.
The fungus kingdom encompasses an enormous diversity of taxa with varied ecologies, life cycle strategies, and morphologies ranging from single-celled aquatic chytrids to large mushrooms. However, little is known of the true diversity of Kingdom Fungi, which has been estimated at around 1.5 million species, with about 5% of these having been formally classified.
The English word fungus is directly adopted from the Latin Fungus (mushroom), used in the writings of Florace and Pliny. This in turn is derived from the Greek word Sphongos (Sponge), which refers to the macroscopic structures and morphology of mushrooms and molds. The discipline of biology devoted to the study of fungi is known as mycology, which is regarded as a branch of botany, even though studies have shown that fungi are more closely related to animals than to plants.
The Kingdom Fungi includes some of the most important organisms, both in terms of their economic and ecological roles. For instance fungi by breaking down the dead organic material in the environment continue the cycle of nutrients through ecosystems. Furthermore, most vascular plants could not grow without the symbiotic fungi that inhabit their roots and supply essential nutrients. Fungi have been essential in providing many breakthrough drugs, such as penicillin and more sophisticated antibiotics. Other fungi have given us wonderful foods such as mushrooms, morels and the much desired truffle. From fungi we also obtain our breads, beers, and champagnes. However, with the Kingdom Fungi also comes the negative.
Fungi are also responsible for a number of diseases of both plant (leaf, root and stem rot, rusts and smuts) and varied diseases in animals and humans. Precisely because fungi are more genetically and chemically similar to animals than any other organisms, fungal diseases are very difficult to treat.
We now turn to one fungal problem in particular relating to human health. Onychomycosis is a fungal infection of the fingernail or toenail. Onychomycosis is a progressive, recurring fungal infection that initially first occurs in the nail bed and progresses to the nail plate. The main structural components of the nail include the lateral and proximal folds, cuticle, matrix, plate and hyponychium. The proximal nail fold is located at the proximal end of the visible nail plate where it folds over itself. The horny layer of the proximal nail fold is called the cuticle. The cuticle consists of modified stratum corneum that originates at the junction of the dorsal and ventral epithelial surfaces and proceeds along the nail surface. The cuticle protects the matrix from exposure to foreign material, including infection from microorganisms. The matrix is the growth center of the nail and is located at the proximal end under the cuticle. This site contains basal cells that migrate into the nail plate, where they divide and differentiate, forming the hard, keratinized component of the nail plate. The nail plate is the largest structure of the nail unit and is attached to the top of the nail bed. This transparent structure is gradually replaced as it grows out. The structure is completely renewed every 6 months on fingers and every 10 to 18 months on toes. The nail grows faster on longer digits, digits that are used most often and on traumatized nails. The nail bed is located under the nail plate and consists of epidermal grooves and ridges that contain small blood vessels. The dermis of the nail borders bone (the phalanx) rather than subcutaneous tissue.
Fungal infections usually invade the nail (between the nail plate and the nail bed) through an opening in the subungual space of the hyponychium, near the distal groove. The infection starts distally, then progresses proximally. However, trauma to the cuticle may also permit entry of fungal organisms.
The types of microorganisms that cause onychomycosis can be broadly classified into 2 groups: dermatophytes and nondermatophytes. Dermatophytes are fungi that infect keratinous tissue. Nondermatophytes that cause onochomycosis are either yeasts or molds. Dermatophytes are by far the most common causative pathogens of onychomycosis.
The nail provides the perfect place for the fungus and protects it while it grows, since fungi love damp, warm, dark places, the nails of our fingers and toes are very effective barriers. This barrier makes it quite difficult for a superficial infection to invade the nail. However, once an infection has invaded that same barrier that was so effective in protecting us against infection now works against us, making this type of fungal infection very difficult to treat.
Onychomycosis is not an uncommon disease. This type of infection accounts for approximately half of all nail disorders and one third of cutaneous fungal infections in the United States. Studies suggest that the number of persons affected is apparently on the rise. This rise may be attributed to many factors among them the aging population. Some studies suggest that 48% of the population may be infected by age 70. The increasingly higher occurrence of onychomyosis may also be attributable to the greater use of immunosuppressive drugs, the increasing number of people infected with HIV, the increasing exposure to pathogens in public swimming pools and spas, and high heels and tight fitting shoes in fashion styles. The growth of low cost nail salons that may not always properly disinfect nail instruments thoroughly between clients is also attributing to the increasing occurrence of onychomycosis in many countries.
The problem with onychomycosis is aggravated by the fact that it is very contagious and easily passed from person to person. In fact, many infected people are under the impression that the infection will resolve spontaneously and go without any treatment while infecting other people. On the other hand, onychomycosis is notoriously difficult to treat and long treatment periods have typically been required to cure the infection using conventional drugs and techniques. It is not uncommon for patients to simply give up before that infection has been eradicated.
The dermatophyte fungus that causes the onychomycosis infection is ubiquitous. It rarely remits spontaneously and typically spreads to involve the entire nail anatomy. Unfortunately, onychomycosis frequently spreads to other digits, and sometimes spreads to other sites and to other family members as well as others that come in contact with the infected person or infected articles which are contaminated by the infected person.
Participants in numerous athletic activities of varied nature are much more susceptible to onychomycosis. Some of these athletic activities include: long distance running, ballet dancing, golf, and soccer. A wide array of preexisting medical conditions also leads to a higher level of susceptibility to being infected with onychomycosis. Some of these medical conditions include: diabetes mellitus, blood circulation disorders (including varicose veins in the legs, pallor of fingers and toes, and poor peripheral circulation), and genetic susceptibility associated with Down's syndrome, Raynaud syndrome, and Cushing's syndrome. Cancer patients that are being treated with chemotherapy and organ transplant recipients on anti-rejection drugs are also in a high risk group.
Nail trauma is a frequent cause of onychomycosis. Individuals in trades and professions that involve the wearing of sports or safety shoes are also at higher risk. Men are more prone to onychomycosis than women. The reasons for this gender difference are not clear but may involve higher occurrence of nail trauma that results from professional and athletic activities. Social and/or genetic factors may also play a role.
Nail fungus is more than just a cosmetic problem. Many people complain of discomfort in walking, pain, or limitation of their work or other activities. Gross distortion and dystrophy of the nail may cause trauma to adjacent skin and may lead to secondary bacterial infection. In several studies, patients with onochomycosis reported significantly poorer general health, mental health, social functioning, and body pain than did people without this nail infection. Psychosocial limitations included fear of social situations that exposed on infected fingernail or toenail.
In immuno-compromised people, there is a great risk that this infection will disseminate. Although onychomycosis causes some degree of morbidity for healthy individuals it is especially pronounced in high risk patients such as diabetics, patients with HIV, AIDS or other types of immunosuppressant, including transplant recipients, and patients on long term corticosteroid therapy.
Onychomycosis poses a greater risk to diabetic patients because of the possible sequelae. In particular, high risk diabetic patients with compromised lower extremities and severe neuropathy are at increased risk of developing complications from onychomycosis. Most notably impaired sensation can make many diabetics less aware of minor abrasions and ulcerations on their feet that may be caused by trauma, from poor nail grooming or by the sharp brittle or infected nails characteristic of onychomyosis. These lesions in turn may develop into serious paronychia, cellulites or bacterial infections, and contribute to the severity of the diabetic foot. Osteomyelitis can also result from neglected, infected nail bed erosion in diabetic patients because of the close proximity of the nail bed to the underlying bone. Nearly 18% of gangrene and 10% of foot ulcers in people can be attributed to onychomycosis. Thus, diabetics with onychomycosis should treat it quickly as it may lead to much greater, catastrophic results.
Everyone should seek treatment of a nail fungus as soon as one is suspected. Symptoms of nail fungus can include nail changes such as, brittleness, change in nail shape, crumbling of the outside edges of the nail, debris trapped under the nail, loosening or lifting up of the nail, loss of luster or shine, white spots, thickening of the nail or white or yellow streaks on the side of the nail. Much more rarely, a black strip or spot is present.
Current treatment for ocychomycosis include mechanical debridement, oral drugs, topical drugs, removal of nail and laser treatments. Mechanical debridement is a traditional podiatric approach that requires time, specialized instruments, and experience. The goal of this approach is to reduce pressure and fungal load by mechanically reducing nail thickness. Since mechanical debridement removes a large portion of fungal material it has potential to enhance the effectiveness of other therapies. However, it does have its limitations. It does not eradicate the infectious pathogens, and it must be repeated as the nail grows until the infection is gone.
Oral antifungal medications are often prescribed as first -line treatments for nail fungus. These systemic drugs reach the infected nail via the peripheral circulation. Though antifungal medications have improved it has been suggested that as many as 25% to 40% of onychomycosis cases are classified as treatment failures in clinical practice. In addition these oral drugs have many adverse side affects including headache, gastrointestinal symptoms such as diarrhea, dyspepsia, abdominal pain, constipation, nausea and flatulence; dermatological symptoms such as rash, pruritus and urticaria. Additionally these oral antifungal drugs may affect the liver, therefore liver function and white cell counts should be assessed at baseline and periodically during treatment. Neutropenia and transient taste disturbance may also result. Another downside to oral antifungal medication is the financial impact for the patient as these oral antifungal drugs can be quite expensive.
Current topical antifungal therapy is effective for the treatment of onochomycossis in some cases. This approach involves the direct application of an antifungal drug to the infected nail. These drugs are thought to diffuse through the nail plate to reach the site of infection, where they eradicate fungal organisms. These over the counter creams and ointments generally do not help treat this condition.
Removal of the nail involves the removal of the affected nail plate; this may be performed surgically or chemically. This approach allows growth of a new nail but can traumatize the nail bed, which may affect the appearance of the new nail. Total nail removal causes great discomfort to the patient and therefore is discouraged. Only in the most severe cases should this method be recommended.
Practitioners have been using lasers for toenail fungus since 2009. However, podiatrists using this method disagree greatly on its effectiveness both medically and from the standpoint of cost. The treatment consists of the practitioner aiming a laser beam at the patient's toenail to kill the organisms that cause the fungus. The nails are not immediately clear after the treatment, which takes up to an hour and the patient must wait for the fungus free nail to grow out which can take up to about 18 months. Multiple laser treatments are frequently required and the total cost of such treatments can preclude them from being a possibility for many patients. In addition to this the high cost of laser treatments is generally not covered by insurance because it is considered to be an aesthetic procedure.
Considering the problems associated with the current methods of treatment for nail fungus something more ideal needs to be found. Georgeanne Botek, DPM Department of Orthopedic Surgery at The Cleveland Clinic, suggests that the ideal anti fungal treatment would be broad spectrum, taken up and incorporated into the nail matrix, diffusing through the epithelium of the nail bed to reach the nail bed hyperkeratosis, and penetrating into the ventral surface of the plate. Additionally, it would be effective, with high rates of clinical cure (ascertained by laboratory testing, fungal culture) and a low rate of relapse and effective when used short term (the duration of new nail re-growth) and have few in any adverse effects and adverse drug interactions. It should also, of course, be cost effective.